Mechanistic Study of Alkyne Insertion into Cu–Al and Au–Al Bonds: A Paradigm Shift for Coinage Metal Chemistry

In this work, the mechanism of the insertion reaction of 3-hexyne into Cu–Al and Au–Al bonds in M–aluminyl (M = Cu, Au) complexes is computationally elucidated. The mechanism is found to be radical-like, with the Cu–Al and Au–Al bonds acting as nucleophiles toward the alkyne, and predicts a less efficient reactivity for the gold–aluminyl complex. The proposed mechanism well rationalizes the kinetic (or thermodynamic) control on the formation of the syn (or anti) insertion product into the Cu–Al bond (i.e., dimetallated alkene) which has been recently reported. A comparative analysis of the electronic structure reveals that the reduced reactivity at the gold site—usually showing higher efficiency than copper as a “standard” electrophile in alkyne activation—arises from a common feature, i.e., the highly stable 6s Au orbital. The relativistic lowering of the 6s orbital, making it more suitable for accepting electron density and thus enhancing the electrophilicity of gold complexes, in the gold–aluminyl system is responsible for a less nucleophilic Au–Al bond and, consequently, a less efficient alkyne insertion. These findings demonstrate that the unconventional electronic structure and the electron-sharing nature of the M–Al bond induce a paradigm shift in the properties of coinage metal complexes. In particular, the peculiar radical-like reactivity, previously shown also with carbon dioxide, suggests that these complexes might efficiently insert/activate other small molecules, opening new and unexplored paths for their reactivity.

For complex 1-Au, we have demonstrated that the nucleophilic behavior of the electron-sharing, weakly polarized Au−Al bond combined with Al acting as an electrophile is the driving force for the CO 2 insertion reactivity occurring via a cooperative radical-like mechanism. 5−8 The main interaction in the CO 2 insertion process has been shown to be electron donation from the Au−Al σ bond toward the CO 2 LUMO, assisted by a secondary interaction where electron donation occurs from the CO 2 HOMO toward the Al center (mostly an empty 3p z orbital). These unique Au−Al electron-sharing bond nature and radical-like mechanism features, which are uncommon in gold(I) chemistry, make these species suitable candidates for insertion chemistry. In the same context, we have also analyzed the Cu−Al bond in 3-Cu, which has been found to have an analogous electron-sharing nature with, however, a slight Cu(δ + )−Al(δ − ) polarization that may lead to subtle differences in their reactivity. 5 More recently, internal alkyne insertion into the Cu−Al bond of the copper−aluminyl complex 3-Cu has been experimentally reported, producing (aluminylalkenyl)copper compounds which possess different reactivity at the two derived M−C functions. 9 Complex 3-Cu is able to control the nature of the formed (syn or anti) dimetallated alkenes, with syn isomers accessible through a kinetic control with high selectivity and anti isomers isolable through a thermodynamic control (Scheme 2). The syn dimetallated alkenes (9-Cu, 11-Cu) can give a selective insertion of CO leading to the formation of copper acyl compounds. 9 Strictly related gold silyl 10,11 and boryl 12 complexes have been also experimentally reported to insert alkynes into Au−Si and Au−B bonds. Amgoune and Bourissou reported that alkynes can be activated via insertion into the Au−Si bond of the gold silyl (R 3 P)AuSiR'Ph 2 (R = Ph, Me; R' = t Bu, Ph) systems with exclusively syn stereochemistry. Similarly, Yamashita et al. very recently reported an isomerization of a cis-(2-borylalkenyl)gold complex via a retro-1,2-metalate shift, where the first step is syn insertion of an internal alkyne into the Au−B bond of the [IPrAuB(Ar) 2 ] (IPr = N,N'-bis (2,6-di-iso-propylphenyl)imidazole-2-ylidene; Ar = o-tolyl) gold boryl 13-Au-B complex (Scheme 2). 12 We have recently demonstrated that the Au−Al and Au−B bonds in [LAuX] (L = phosphine, N-heterocyclic carbene (NHC); X = Al(NON), B(o-tol) 2 ) complexes possess a similar electron-sharing nature, with diarylboryl complexes displaying a slightly more polarized bond as Au(δ + )−B(δ − ), which is responsible for a reduced radical-like reactivity toward CO 2 8 (consistent with the reaction of complex [IPrAuB(o-tol) 2 ] with carbon dioxide having not been experimentally reported). 13 The ancillary ligand of gold (phosphine or carbene) has been shown to have a negligible electronic trans effect on the Au−X bond and only a minor impact on the formation of the insertion product, although modification of the steric hindrance at the carbene site may exert a sizable control over the reaction. 8 In this framework, one might surmise that the electronsharing nature of the Au−Al bond in complex 1-Au which allowed to rationalize its reactivity with CO 2 may favor the reaction of complex 1-Au with alkynes analogous to that of complex 3-Cu. A comparative investigation of alkyne insertion in complexes 1-Au and 3-Cu would be relevant to shed light on the metal effect on this reactivity by a detailed comparison between Au−Al and Cu−Al bond nature and reaction mechanisms. As mentioned, a radical-like reactivity is new in gold chemistry, substantially differing from the well-known strong carbophilic Lewis acid behavior of gold complexes toward alkynes. 14 Most of the reactions in which gold catalysts are involved can be classified as nucleophilic additions to a carbon− carbon unsaturated bond (alkynes, alkenes, and allenes), proceeding in a stepwise manner. In typical gold complexes of LAuX type (L = phosphine, carbene; X = counterion), the facile substitution of X with the alkyne substrate (pre-equilibrium Scheme 1. Reactions of Gold−Aluminyl 1-Au, Silver−Aluminyl 2-Ag, and Copper−Aluminyl 3-Cu Complexes with CO 2 Leading to Corresponding 4-Au, 5-Ag, and 6-Cu Insertion Products step) allows for a η 2 coordination of the CC triple bond to the Au center which, acting as an electrophile, activates it for the subsequent nucleophilic attack by Nu−H (for instance, alcohols, water, amines, etc.), with the formation of vinyl gold intermediates and subsequent cleavage of the gold−carbon bonds by a proton (protodeauration step), to give the desired products and regenerate the catalyst. 15−19 Remarkably, the nucleophilic attack commonly occurs on the Au−CC π complex anti to gold, affording an organogold complex with trans arrangement of the nucleophile and gold center (outer-sphere mechanism, Scheme 3), as supported by several experimental and computational studies. 15−27 Alternatively, the nucleophilic attack has been proposed to involve coordination of the nucleophile to gold and syn insertion of the substrate into the Au−Nu bond, leading to cis vinyl gold intermediates (inner-sphere mechanism, Scheme 3). However, no direct unambiguous evidence for the inner-sphere mechanism has been reported to date. 28−32 Cu-catalyzed reactions of internal alkynes for the synthesis of different valuable alkenes and heterocycles have also appeared in the literature in the last decade and they follow analogous mechanisms, with the functionalization occurring via both an inner-and an outersphere mechanism. 33 However, the M−alkyne (M = Cu, Au) bond energies vary generally in the order Cu < Au, indicating a more efficient activation of the triple bond by gold complexes, due to their higher electrophilicity. In addition, dinuclear gold (and heterobimetallic Cu/Au) complexes and their use in catalysis have recently received significant attention and comparative studies of the controversial mono-vs dual-metal-catalyzed pathways have appeared in the literature. 34−39 From a more general perspective, insertion reactions of organic molecules into heterobimetallic M−M' or M−E (E = B, Si) bonds represent an attractive approach to synthetic organic chemistry and industrial catalysis, although examples of this heterobimetallic reactivity are still scarce. [10][11][12]40,41 One challenge in heterobimetallic catalysis is identifying a metal cooperative effect (if any) and its origin through mechanistic investigation, which can provide the necessary insight to understand how these catalysts work and possibly how modifications can be planned to increase both the activity and selectivity.
In this work, we computationally elucidate the mechanism of the experimentally observed alkyne (3-hexyne) insertion reaction into the Cu−Al bond in complex 3-Cu which is compared to that of the analogous model insertion reaction into the Au−Al bond in complex 1-Au. Detailed mechanistic analysis highlights the superior ability of the copper−aluminyl complex in activating (and inserting) the alkyne, leading to a more efficient formation of the syn product. The superior activity of 3-Cu with respect to 1-Au is found to be consistent with the relativistic stabilization of the gold valence atomic orbitals, in particular the 6s orbital, which is commonly known to enhance the electrophilicity of gold complexes and which, in this case, is responsible for a less efficient nucleophilic behavior of the gold− aluminum electron-sharing bond, thus inducing a paradigm shift in the coinage metal chemistry.
■ RESULTS AND DISCUSSION Reaction Mechanism of the Alkyne Insertion into the Cu−Al Bond. The free-energy profile for 3-hexyne insertion into the Cu−Al bond of complex 3-Cu is illustrated in Figure 1. It has been calculated using the same computational setup as that employed in ref 5 for the insertion reaction of CO 2 into the Au−Al bond in complex 1-Au (see the Computational Details Section). Optimized structures of stationary points along the paths are also sketched with selected geometrical parameters in Figure 2.
Starting from the reactant complex RC anti , where the substrate CC triple bond is oriented perpendicular to the Cu−Al bond, alkyne insertion occurs with an activation free-energy barrier ΔG ≠ = 24.3 kcal/mol (via TSI anti ) leading directly to the formation of the anti insertion product (PC anti ) (red line profile). The process is exergonic with ΔG = −12.8 kcal/mol. Reactant complex RC syn , featuring the CC triple bond parallel to the Cu−Al bond, allows for alkyne insertion (blue line profiles) occurring both at the Al (via TSI syn , ΔG ≠ = 14.3 kcal/ mol) and at the Cu (via TSI syn Cu , ΔG ≠ = 6.2 kcal/mol) sites and leading to a stable intermediate species PC' syn (ΔG = −11.6 kcal/mol) which, upon Cu−Al bond stretching, yields a less stable syn insertion product (PC syn , ΔG = −5.0 kcal/mol). This reaction mechanism is in good agreement with the experimental finding that formation of the syn dimetallated alkenes is under kinetic control (lower activation barriers are calculated for syn insertion). Notably, in the TSI syn and TSI syn Cu structures ( Figure 2), both the Cu and Al sites are involved in a concerted mechanism, preferentially starting at the Cu site. As for the thermodynamic control for the formation of the anti isomer, comparison of the PC syn main geometrical parameters with available X-ray crystallography data (see Figure 2) shows that this species is in good agreement with experimentally reported parameters, thus representing the isolated species, although PC syn is found to be less stable than PC anti by 7.8 kcal/mol (and PC' syn by 6.6 kcal/mol). The interconversion of PC syn to PC anti has been proposed to occur through a C-to-Al migration of an Et group based on the isolated and structurally characterized (NON)AlEt species 9 and in analogy with the reactivity of the boryl gold compound reported by Yamashita et al. 12 Access to anti dimetallated alkene has been investigated through a twostep process via TS side and TS syn/anti transition states (gray line, Figure 1), i.e., thorough isomerization of the PC syn species. The calculated barrier for the first step (denoted as "side reaction") leading to (NON)AlEt and copper acetylide co-product PC side is ΔG ≠ = 24.3 kcal/mol, indicating that the migration of the Et group is viable from PC syn along the path for the syn/anti conversion. Formation of PC side is exergonic by 4.7 kcal/mol and dissociation into (NON)AlEt and [ t Bu 3 PCuCCEt] separated species requires only 2.0 kcal/mol (see Figure S1). The PC side conversion to PC anti involves the Et group migration to the alkyne (via TS syn/anti ) with a high activation energy ΔG ≠ = 31.8 kcal/mol. These results indicate that the rate-determining step is the isomerization from PC side to PC anti , which is consistent with the more forcing experimental conditions (heating to 45°C for 6 h) needed to access the anti insertion product and with the experimental observation that (NON)AlEt can be isolated from the reaction mixture, whereas assignment of anti dimetallated alkene (PC anti ) could not be confirmed crystallographically for 3-hexyne. The preferential formation of PC syn via TSI syn Cu with respect to the other pathways described above can be rationalized by analyzing the evolution of the electronic structure along the reaction path. In particular, the analysis of the alkyne−complex interaction at the three initial transition states for each path (i.e., TSI syn , TSI syn Cu , and TSI anti ) using energy decomposition analysis (EDA), 42 natural orbitals for chemical valence (NOCV), 43 and charge-displacement (CD) 44−46 approaches, in combination with the activation strain model 47−49 (ASM, see the Methodology section in the SI for details on these approaches), allows to gain quantitative insights into the factors controlling the reported reactivity.
As depicted in Figures 3 and S2−S7 and Table S1 in the SI, the alkyne−complex interaction at TSI syn , TSI syn Cu , and TSI anti for the copper−aluminyl complex is, on a qualitative ground, of analogous nature.
Despite a different geometrical rearrangement of both the complex and alkyne moieties, the NOCV analysis reveals a qualitatively analogous interaction at the three TSs, where the main component Δρ 1 ' identifies a charge transfer arising from the electron-sharing Cu−Al bond (as it can be inferred by the large contribution of the σ Cu−Al centered HOMO of the complex in all cases) toward the π* LUMO of the alkyne fragment ( Figures S2, S4, and S6). A second significant component of the complex−alkyne interaction for all TSs can be observed (Δρ 2 '), which is also qualitatively analogous in all cases and features a reverse alkyne-to-complex charge transfer toward an unoccupied molecular orbital of the complex with large contributions from the empty Al 3p z atomic orbital ( Figures S3, S5, and S7). It is worth noting that the alkyne− complex interaction scheme discussed here is highly reminiscent of that previously reported for the [ t Bu 3 AuAl(NON)]−CO 2 interaction, 5−8 indicating a general scheme for the interaction of this class of complexes with small molecules.
Despite these evident qualitative analogies, on a quantitative ground, the ASM approach (Table S2 in the SI and Figure 4) helps to rationalize the relevant differences between the disfavored anti pathway via TSI anti and the syn pathway, particularly the preferential reactivity via TSI syn Cu .
Although the interaction energy between the alkyne and the complex appears to favor TSI anti with respect to TSI syn Cu (ΔE int is −82.9 and −72.2 kcal/mol, respectively, see Figure 4), thus Inorganic Chemistry pubs.acs.org/IC Article apparently suggesting a more stable TSI anti , the ASM results indicate that the balance between these favorable interactions and the disfavoring distortion penalty is key. As shown in Figure  4, the distortion penalty is much larger in the case of TSI anti (89.4 kcal/mol), while it is lower by almost 30 kcal/mol in the case of TSI syn Cu (62.6 kcal/mol), leading to TSI syn Cu being more stable than TSI anti in terms of relative electronic energy (−9.2 vs 6.4 kcal/mol, respectively), in agreement with the lower freeenergy barrier associated with the syn path (see Figure 1) which determines the kinetic control discussed earlier.  The reason behind the reduced distortion destabilization at TSI syn Cu can be found by inspection of the geometry of the two transition states in Figure 2. While at TSI syn Cu the syn approach of the alkyne leads to a transition state in which the Cu−Al bond is unbroken (the Cu−Al bond length is 2.385 Å), at TSI anti the copper−aluminum bond is cleaved (the Cu−Al bond length is 3.135 Å). Since the Cu−Al bond is a fairly strong bond (the calculated dissociation energy is −78.4 kcal/mol), this leads to a distortion penalty associated with the deformation of the complex which is clearly higher for TSI anti (26.6 kcal/mol, Table   S2) with respect to that for TSI syn Cu (14.9 kcal/mol, Table S2). This difference, combined with the higher energy penalty at the alkyne site (ΔE dist alkyne is 47.7 and 62.7 kcal/mol for TSI syn Cu and TSI anti , respectively) due to the higher degree of alkyne deformation (the C−C bond length is 1.321 vs 1.383 Å for TSI syn Cu and TSI anti , respectively), explains the preferential syn formation from a kinetic standpoint.
Finally, it is worth exploring the nature of the reactivity in relation to the formed products, especially considering that gold−aluminyl complexes have been reported to react with CO 2 with a radical-like reactivity, i.e., with gold and aluminyl fragments behaving as doublet species when capturing CO 2 . 5−8 Based on the scheme previously used for gold− aluminyl complexes, 5−8 we describe the formation of PC syn , PC syn ', and PC anti from both radical doublet [ t Bu 3 PCu]· and [Al(NON)]· and closed shell charged [ t Bu 3 PCu] + and [Al-(NON)] − fragments (see Scheme S1 in the SI). The results, reported in Table S3 in the SI, strongly suggest that a similar radical-like reactivity is also observed for copper−aluminyl reacting with the alkyne. Indeed, the overall formation energy of the products (ΔE) is found to be lower starting from radical fragments (−102.2, −106.9, and −106.9 kcal/mol for PC syn , PC syn ', and PC anti , respectively) with respect to that from the corresponding closed shell fragments (−131.6, −136.3, and −136.3 kcal/mol for PC syn , PC syn ', and PC anti , respectively), thus indicating the higher stability of the radical fragments, in strict analogy with the reaction of 1-Au with CO 2 . This finding  Inorganic Chemistry pubs.acs.org/IC Article further elucidates that (i) the alkyne insertion occurs neither with an outer-nor an inner-sphere but more properly via a radical-like mechanism relying on a nucleophilic Cu−Al bond as the driving force and (ii) the reactivity mode previously found for gold−aluminyl complexes with CO 2 (i.e., a cooperative radical-like reactivity) emerges here as a more general paradigm for coinage metal−aluminyl complexes (and electron-sharing M−Al bonds) efficiently reacting with small molecules. Reaction Mechanism of the Alkyne Insertion into the Au−Al Bond. The free-energy profile for 3-hexyne insertion into the Au−Al bond of complex 1-Au is illustrated in Figure 5, with the optimized structures of stationary points along the paths sketched with selected geometrical parameters in Figure 6.
The reaction paths are qualitatively similar to those for 3-Cu, with some relevant quantitative differences. Alkyne anti insertion occurs with an activation free-energy barrier of 32.3 kcal/mol (via TSI anti ) leading directly to the formation of the anti insertion product (PC anti ) (red line profile, ΔG = −5.8 kcal/ mol). Analogously, the syn insertion via TSI syn (ΔG ≠ = 16.9 kcal/mol) or via TSI syn Au (ΔG ≠ = 27.4 kcal/mol) leads to a stable intermediate species PC' syn (ΔG = −6.6 kcal/mol) which, upon Au−Al bond stretching, yields a less stable syn insertion product (PC syn , ΔG = −0.3 kcal/mol). As a result, formation of the syn dimetallated alkenes occurring at the Au−Al site is similarly predicted under kinetic control, with a higher activation barrier compared to that calculated for 3-Cu (16.9 vs 6.2 kcal/ mol). Similarly, in the TSI syn and TSI syn Au structures (Figure 6), both the Au and Al sites are involved, reflecting again a cooperative effect of the two centers in the alkyne insertion, with a more relevant role of Al. Notably, in the RC syn structure, the Au−Al bond distance (2.418 Å) is close to the experimental value reported for complex 1-Au (2.402 Å) 1 and slightly shorter than the sum of the single-bond covalent radii of Au and Al (2.50 Å). 50 Preferential formation of the syn product via kinetic control can be explained on the basis of what was discussed in the previous section for 3-Cu, i.e., the enhanced distortion penalty at TSI anti due to a substantially broken Au−Al bond (Au−Al bond length is 3.212 Å, see Figure 6) leading to a higher activation barrier (see Table S5 in the SI for the ASM results).
Analogously to 3-Cu, PC syn has a lower stability than PC anti (by 5.5 kcal/mol) and PC' syn (by 6.3 kcal/mol), and, remarkably, the RC syn -to-PC syn conversion is practically thermoneutral, thus suggesting a possibly reversible reaction with a PC syn that experimentally may be hardly isolable.
Interestingly, the formation of the syn products is predicted to occur via different paths for 3-Cu and 1-Au. Whereas the former is predicted to form more favorably the corresponding PC' syn via TSI syn Cu (i.e., via a transition state where the alkyne is coordinated to the metal in a roughly η 2 fashion) with an activation barrier of 6.2 kcal/mol, the kinetically favored path for 1-Au is predicted to be via TSI syn , which features a lower activation barrier (ΔG ≠ = 16.9 kcal/mol) with respect to that via TSI syn Au (ΔG ≠ = 27.4 kcal/mol), thus suggesting that the alkyne η 2 -like coordination to Au leads to a less stable transition state.
EDA, CD, NOCV, and ASM approaches help to shed light on these differences (see Tables S4, S5, and Figures S8−S13 in the SI for the complete results). On a qualitative ground, the alkyne−complex interaction appears to be unaffected by  (see Figures S8, S10, and S12 in the SI). In all cases, a second component (Δρ 2 ') is observed which consists of a charge transfer from the alkyne HOMO toward the LUMO of the complex (see Figures S9, S11, and S13 in the SI). On a quantitative ground, however, the differences concerning the stability of TSI syn Cu and TSI syn Au , which determine the different preferential paths for 3-Cu and 1-Au, respectively, become evident. In particular, comparison of ASM results (see Tables 1, S2, and S5 in the SI) clarifies that the interaction between the substrate and the complex contribution (ΔE int ) is found to be the determining factor driving their different stability.
As shown in Table 1, while both TSI syn Cu and TSI syn Au feature analogous distortion penalties (62.6 and 64.0 kcal/mol, respectively), the stabilizing interaction contribution is different (−72.2 vs −49.8 kcal/mol, respectively), favoring an overall more stable TSI syn Cu (ΔE is −9.6 and 14.2 kcal/mol, respectively). The EDA-NOCV approach allows to decompose the interaction energy term ΔE int , showing in detail that the complex−alkyne interaction mainly differs at the two TSs due to an orbital interaction increase (ΔE oi is −187.6 vs −176.0 kcal/ mol for TSI syn Cu and TSI syn Au , respectively) and, in particular, to a more energetically stabilizing complex-to-alkyne charge transfer (ΔE oi 1 is −140.4 vs −127.2 kcal/mol for TSI syn Cu and TSI syn Au , respectively). The Pauli repulsion component also differs in the two TSs, being significantly lowered at TSI syn Cu (ΔE Pauli is 346.1 vs 357.0 kcal/mol for TSI syn Cu and TSI syn Au , respectively).
The larger Pauli repulsion contribution at TSI syn Au may be rationalized on the basis of the more spatially extended 5d Au compared to the 3d Cu orbitals, as recently highlighted by Toste, Head-Gordon and co-workers. 51 On the other hand, the increased orbital energy stabilization coming from the increased ΔE oi (and in particular ΔE oi 1 ) at TSI syn Cu with respect to TSI syn Au can be explained by analyzing the HOMO (i.e., the main filled molecular orbital of the complexes involved in the Δρ 1 ' component) of the metal−aluminyl complexes at their corresponding transition state structure, as shown in Figure 7.
From Figure 7a, the composition of the 3-Cu HOMO at the TSI syn Cu structure features contributions from copper 4s, 4p x , and 3d xz atomic orbitals which sum up to 33.6% (8.4, 14.7, and 10.5% contributions from Cu 4s, 4p x , and 3d xz orbitals, respectively). Coupled with contributions from Al (20.3%), overall the 3-Cu HOMO at TSI syn Cu is mostly centered on the two metals (53.9%), quantitatively rationalizing the cooperative behavior of the two metals in the reported reactivity. Concerning 1-Au (Figure 7b), while the Al orbitals give analogous contributions (20.5%), the 1-Au HOMO at TSI syn Au has less coinage metal character (overall 26.2%, with 8.7, 9.4, and 8.1% contributions from Au 6s, 6p x , and 5d xz atomic orbitals, respectively). This different composition leads to an overall lower bimetallic character of the HOMO (46.7%). As a result, the reactivity of 1-Au via TSI syn Au is less efficient and this can be quantitatively inferred also by the energy of the HOMO, which is more stable (and thus, according to the frontier molecular orbital theory, less reactive) for 1-Au (−3.922 eV) than for 3-Cu (−3.787 eV, see Figure 7a,b).
These results can be rationalized on the basis of the radicallike reactivity of the metal (and aluminyl) fragments and metal's atomic orbitals. As shown in Scheme S1 and Tables S3 and S6 in the SI, the product formation is favored by starting from [ t Bu 3 PM]· (M = Cu, Au) and [Al(NON)] · radical fragments, suggesting a radical-like reactivity of both gold− and copper− aluminyl complexes, also consistent with gold's valence 5d 10 6s 1 configuration in gold−aluminyl complexes we recently discussed. 52 Upon spin density analysis on the two isolated metal fragments at the geometry they have in TSI syn Cu and TSI syn Au (Figure 7c,d), clear differences emerge between gold and copper. The unpaired electron in the radical [ t Bu 3 PCu] · fragment is highly localized on Cu (0.89 e) with only a small delocalization on P (0.10 e). Conversely, the unpaired electron on [ t Bu 3 PAu] · is less localized on Au (0.78 e) and more delocalized on P (0.21 e). As a result, the unpaired electron on Au is less available for the reactivity with 3-hexyne at the nucleophilic site, leading to a reduced bimetallic character and to a lower-energy and less reactive HOMO with respect to Cu. This decreased availability of the 6s 1 electron on gold is consistent with the relativistic stabilized 6s orbital in Au (−5.678 eV), which is remarkably close in energy to the 3p x atomic orbital of the ligand's phosphorus (−5.506 eV), leading to an efficient overlap and delocalization of the unpaired electron. By contrast, the copper 4s orbital is at higher energy (−4.640 eV), which reduces the overlap with the P orbital and the delocalization toward the ligand, and, consequently, it makes the electron at the copper site more available for the reaction with 3-hexyne. Interestingly, the picture we describe here is well known in the framework of coinage metal chemistry. It is widely accepted that many of the unique properties of gold complexes, such as the high electrophilicity and carbophilicity, can be ultimately attributed to the relativistic enhanced stability of the 6s orbital of Au, at a variance with the less remarkable electrophilicity of analogous linear copper complexes, featuring higher-lying 4s orbitals. 14 However, since copper− and gold−aluminyl complexes display a nucleophilic reactivity, where the M center also plays an active role, here the same features penalize gold with respect to copper and explain the more favorable reactivity of 3-Cu with the alkyne substrate.
This unconventional situation is not uniquely related to the first part of the syn path, but it affects the whole reaction path. For instance, the reduced ability of gold in the aluminyl complex to interact with the alkyne has been investigated by optimizing a "reactant-like" species with the alkyne coordinated to Au and Cu in a η 2 mode (see RC Cu and RC Au in Figure S1 in the SI) which shows a much more unstable complex (ΔG = 18.0 kcal/mol with respect to the separated reactants) formed by 1-Au compared to that formed by 3-Cu (ΔG = 8.0 kcal/mol). Furthermore, at variance with 3-Cu, for 1-Au isomerization of the PC' syn to PC anti species can directly occur via the TS' syn/anti transition state (green line, Figure 5) with a free-energy barrier ΔG ≠ = 16.2 kcal/mol, remarkably close to that for the formation of PC' syn (ΔG ≠ = 16.9 kcal/mol). Attempts to calculate a similar direct path for 3-Cu have led to a minimum energy species with a similar structure to that of TS' syn/anti (see PC' anti in Figure S1 in the SI), representing an additional isomer product of the alkyne insertion reaction.
For the syn/anti conversion through the two-step path, a higher activation barrier for the first step ("side reaction") leading to (NON)AlEt and gold acetylide co-product PC side has been calculated (ΔG ≠ = 31.1 kcal/mol), indicating that the migration of the Et group is not the preferred route to PC anti . In addition, formation of PC side is endoergonic by 6.2 kcal/mol and dissociation into (NON)AlEt and [ t Bu 3 PAuCCEt] separated species releases 2.5 kcal/mol (see Figure S1). Comparison between the corresponding PC side thermodynamic stabilities for 3-Cu and 1-Au (−9.7 vs +5.9 kcal/mol) gives further indirect evidence supporting a less reactive gold site at 1-Au, while 3-Cu is capable of more strongly interacting with unsaturated CC bonds in this uncoventional nucleophilic reactivity. Finally, the PC side conversion to PC anti involving the Et group migration to the alkyne (via TS syn/anti ) has an activation energy of ΔG ≠ = 25.1 kcal/mol. As a result, one can expect that alkyne insertion into 1-Au would furnish a possibly isolable anti insertion product, with the syn product and the side (NON)AlEt product which could be more difficult to isolate and characterize, unless more forcing experimental conditions (higher temperatures and longer reaction times) are used.
This detailed mechanistic and orbital picture provides evidence that the exceptional gold Lewis acid standard reactivity (i.e., the ability of gold to promote insertion of π substrate through an inner-sphere or outer-sphere mechanism, see Scheme 3a,b) is switched in the nucleophilic M−Al scenario. This is consistent with neither an inner-or an outer-sphere mechanism, but it is best described as a cooperative radical-like mechanism (see Scheme 3c), where the actual nucleophile is the metal−aluminyl bond, analogously to what happens in the reactivity with carbon dioxide. This new mode of chemical reactivity by coinage metal complexes toward small molecules opens new perspectives beyond the framework of conventional properties, reactivity, and chemical behavior of coinage metal complexes.

■ CONCLUSIONS
In this work, the reaction mechanism of the alkyne insertion into the Cu−Al bond has been computationally investigated, based on the reported experimental characterization of the reactivity of a copper−aluminyl complex toward 3-hexyne.
The reaction mechanism we find here for the Cu−Al complex nicely agrees with the experimental observations. The calculations predict the activation barrier leading to the syn insertion product, where the alkyne approaches the complex Inorganic Chemistry pubs.acs.org/IC Article closely to the copper site, to be significantly lower than that leading to the anti insertion product, in agreement with the experimentally observed kinetic control over syn product formation. Electronic structure analysis rationalizes the preferential syn formation, showing that the anti path is disfavored due to the substantial copper−aluminyl bond breaking occurring at the first transition state, which increases the distortion penalty and, consequently, the associated activation barrier. The reaction mechanism calculated for the gold−aluminyl complex is qualitatively similar, predicting analogous kinetic control and preferential syn product formation due to energy penalty associated to early Au−Al bond breaking along the anti reaction path. However, alkyne insertion into the Au−Al bond is expected to furnish a less stable syn product, via an almost thermoneutral step, which could be more difficult to isolate and characterize. Interestingly, the mechanism reported here shows that the reaction is predicted to be less efficient for gold than for copper, in sharp contrast with the more efficient electrophilic reactivity of gold complexes toward unsaturated substrates. Extensive electronic structure analysis demonstrates that, in strict analogy with the reactivity reported for gold−aluminyl complexes toward CO 2 , the driving force of the complex−alkyne interaction is the charge transfer from the electron-sharing copper− and gold−aluminyl bonds toward the π* LUMO of the alkyne. The Cu−Al and Au−Al bonds act as actual nucleophilic sites for the reaction, leading to a cooperative radical-like metal− aluminyl reactivity.
This nucleophilic behavior of M−Al bonds leads to a switch in the well-established paradigm for "standard" electrophilic reactivity at the coinage metal site toward unsaturated substrates. Upon thorough analysis, the generally accepted factor determining superior electrophilicity of gold complexes in this context (i.e., the relativistic stabilized valence 6s orbital) is found to lead here to a less nucleophilic Au−Al bond (where the valence Au configuration is close to 6s 1 ), leading to a less efficient charge transfer toward the alkyne and, in turn, to a less efficient reactivity.
These findings show that these new classes of copper and gold complexes bearing new-generation aluminyl ligands represent a new chapter in the coinage metal chemistry, where the nucleophilic behavior of the metal−aluminyl bonds induces a paradigm switch of established electronic features and, consequently, different trends in the reactivity with wellknown substrates such as alkynes. Furthermore, the results reported here, showing a cooperative radical-like reactivity of the M−Al complexes toward 3-hexyne analogous to that toward carbon dioxide, suggest that these complexes may efficiently react with a range of other small molecules, opening new and unexplored paths for the reactivity of coinage metal complexes.

■ COMPUTATIONAL DETAILS
All geometry optimizations and frequency calculations on optimized structures (minima with zero imaginary frequencies and transition states with one imaginary frequency) for the alkyne insertion into the [ t Bu 3 PMAl(NON)] (M = Cu,Au) complexes have been carried out using the Amsterdam Density Functional (ADF) code 53,54 in combination with the related Quantum-regions Interconnected by Local Description (QUILD) program. 55 The PBE 56 GGA exchange-correlation (XC) functional, the TZ2P basis set with a small frozen core approximation for all atoms, the ZORA Hamiltonian 57−59 for treating scalar relativistic effects, and the Grimme's D3-BJ dispersion correction were used. 60,61 Solvent effects were modeled employing the conductor-like screening model (COSMO) with the default parameters for toluene as implemented in the ADF code. 62 The same computational setup has also been used for the EDA, CD-NOCV, and ASM calculations and for computing the radical reactions between [Al(NON)], [EtCCEt], and [ t Bu 3 PM] fragments. This protocol has been used successfully in refs 1, 5 to study the The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.inorgchem.2c03713.
Methodology, supporting tables (EDA results for 3-Cu and 1-Au, ASM results for 3-Cu and 1-Au, and analysis of the products formation from copper and aluminyl fragments and from gold and aluminyl fragments), figures (optimized structures with Cu/Au−alkyne direct interaction and NOCV isosurfaces of the main interactions at the TSs for 3-Cu and 1-Au) and scheme for the products formation via metal fragments, and xyz coordinates of all structures (PDF)